Semple Laboratory: Developmental Neurotrauma

Researcher

Research Overview

Brain injuries in young children often results in debilitating and chronic consequences, including psychosocial and neurocognitive deficits which may persist or emerge as the brain matures. However, the biological mechanisms that underlie poor long-term outcomes following traumatic injury to the young brain are poorly understood. Overall, our research goal is to better understand how the immature brain responds to injury, with a particular focus on the sub-acute and chronic periods after an injury. Ultimately, this knowledge will allow us to develop novel therapeutic interventions aimed at improving outcomes and quality of life for brain-injured patients.

Several ongoing research projects are centred around this theme, using a range of approaches including molecular and cellular methods, neuroimaging, in vivo electroencephalographic recordings, and behavioural assays. Brain injuries are associated with a heightened risk of developing epilepsy, or recurrent seizure activity that may contribute to progressive neurodegeneration and infer with quality of life. Using a validated mouse model of traumatic injury in the paediatric mouse, we are evaluating the contribution of inflammatory mediators (e.g. interleukin-1, high-mobility group box protein) to seizure susceptibility and aberrant neuroplasticity. Neuroplasticity that occurs after a brain injury may contribute to aberrant excitatory circuitry as well as neurocognitive dysfunction, and the potential role of glial phagocytosis in this process is also being investigated.

One of the most commonly reported consequences of paediatric brain injury is a change in social behaviour, for example, a reduction in social interactions, increased social withdrawal and isolation, and associated psychiatric issues such as depression and anxiety. We have developed a model of paediatric brain injury in which mice develop social behaviour deficits as they age to adults, consistent with the trajectory of social behaviour deficits frequently seen in brain-injured children. Using this model, we are now tackling fundamental unanswered questions about the underlying mechanisms of these behavioural changes after brain injury, including the identification of risk and resilience factors.